Several observations suggest to us that PRL and GH may be involved in the regulation of the hepatic synthesis of carnitine, a substance essential for fatty acid oxidation and ketogenesis. First, hepatic carnitine increases four-fold in late pregnancy and during lactation in the rat, concomitant with a rise in hepatic PRL receptors and plasma PRL. Second, hepatic carnitine is markedly increased in rats bearing a pituitary tumor that produces PRL, GH and ACTH. Third, we have found that feeding glucose to female rats decreases both hepatic carnitine and the hepatic PRL receptors without altering plasma PRL, and glucose administration is known to suppress GH secretion. Fourth, we have observed that the infusion of bPRL or of bGH at a "physiologic" rate increases hepatic carnitine. We hypothesize that PRL and GH may play a role in the maintenance of hepatic carnitine, and that the decrease in hepatic carnitine induced by carbohydrate feeding may be mediated in part by a decrease in hepatic PRL receptors and in plasma GH. The following studies are proposed to examine this hypothesis: 1) To test our theory that the suppressive effect of glucose feeding on hepatic carnitine is mediated by a decrease in PRL receptors, we will study the effect of glucose on hepatic carnitine in hypophysectomized rats devoid of PRL, and in PRL-replaced hypophysectomized rats. 2) To study the mechanism by which glucose feeding decreases hepatic PRL binding and carnitine content, and to examine the relation between PRL binding and carnitine, we will do studies, in vivo and in isolated rat hepatocytes, on the effect of changes in the concentrations of plasma or medium glucose, insulin and glucagon on hepatic PRL receptors and carnitine. 3) We will examine the direct effect of bPRL and bGH on hepatic carnitine by studying the effect of these hormones on carnitine in isolated rat hepatocytes. 4) We will study the effect of bPRL and bGH in the hypophysectomized rat on the carnitine concentration in plasma, skeletal muscle and myocardium, and on the renal clearance of carnitine. These studies may expand our understanding of the metabolism of carnitine, and provide insights into the pathogenesis and possible treatment of those forms of liver, muscle and heart disease in which carnitine deficiency is thought to play a role.